Harlequin syndrome in a patient with probable hemicrania continua and exertional headache - is there a link? a case report.

BACKGROUND: The harlequin syndrome is a rare disorder of the autonomic nervous system characterized by unilateral diminished flushing and sweating of the face following exposure to heat or physical activity. It results from sympathetic dysfunction and most commonly occurs idiopathically. A secondary development due to an underlying pathology (e.g., carotid artery dissection, tumors) must be excluded at first appearance. There is evidence that the cranial autonomic system is involved in the pathophysiology of trigeminal autonomic headaches like hemicrania continua. Therefore, an overlap in the pathophysiology of harlequin syndrome and trigeminal autonomic headache disorders seems plausible. However, the association of a harlequin syndrome with hemicrania continua was never reported. CASE PRESENTATION: This work describes the case of a 42-year-old female patient presenting to our headache unit. The patient reported persisting unilateral headache of the right side of dragging or squeezing character accompanied by trigeminal autonomic symptoms, including lacrimation, nasal congestion, conjunctival injection and Horner's syndrome, and was responsive to treatment with 75mg/d indomethacin. Five months after the initial consultation, the patient noted that the upper right quadrant of her face was pale after jogging. A harlequin syndrome was diagnosed. Further, she developed a short-lasting, bilateral headache of pulsatile character during strenuous exercise consistent with exertional headache. Comprehensive diagnostic evaluations, encompassing cranial and cervical MRI scans, laboratory tests, and biopsies, culminated in the diagnosis of Sjögren's syndrome. This finding suggests that the trigemino-autonomic dysfunction may either be idiopathic or a direct manifestation of Sjögren's syndrome. CONCLUSIONS: This report documents the case of a rare combination of a headache resembling probable hemicrania continua and the harlequin syndrome (and even exertional headache). It illustrates the underlying anatomy of the autonomic nervous system in a clinical context and emphasizes the hypothesis of a pathophysiological link between abnormal sympathetic activity and trigeminal autonomic headaches.

[Progress in the diagnosis and treatment of Congenital insensitivity to pain with anhidrosis].

Congenital insensitivity to pain with anhidrosis (CIPA) is a rare disease which mainly affects infants, children and adolescents. As an autosomal recessive disorder, CIPA is also known as familial autonomic dysfunction type 2. The diagnosis of CIPA mainly relies on clinical observation and genetic testing. Currently there is lack of effective treatment, and it is mainly treated by cooling, anti-inflammatory and strengthened guardianization. This article has reviewed the literature and summarized the research on CIPA and progress made in its diagnosis and treatment, with an aim to improve the understanding of this disorder.

Miliaria crystallina.

Miliaria crystallina (MC) is an uncommon form of a sweat retention syndrome that chiefly affects neonates. It is more common in hot and humid conditions, such as in tropical regions. It commonly presents as clusters of dewdrop-like vesicles on a nonerythematous base that heals with furfuraceous scaling. A clinical diagnosis is often sufficient. The differential diagnosis is wide and varying. One of the hallmarks of MC is its self-limiting nature. The purpose of this review is to increase awareness of this condition among physicians and dermatologists.

Concurrence of Hyperhidrosis and Hypohidrosis in Ross Syndrome.

Ross Syndrome is a rare disorder characterized by tonic pupils, hyporeflexia, and abnormal segmental sweating. The pathophysiology of the disease remains unclear, with either hypohidrosis or hyperhidrosis reported in individual patients. We present the case of a man, aged 57 years, who presented with hyperhidrosis in his right extremities, anhidrosis in the left extremities, and changes in his pupils. The disease was not associated with markers of autoimmune disease, which supports recent research findings on the role of neurodegeneration. The patient's son was exhibiting similar symptoms, which implicates genetic inheritance in the process. A multidisciplinary approach is crucial for the diagnosis and ultimate management of patients with Ross Syndrome.

Ross syndrome with chronic cough and RF positivity: a case report.

Ross syndrome is a rare disorder of unknown etiology, characterized by the triad of segmental anhidrosis, tonic pupil, and areflexia/hyporeflexia. Ross syndrome is thought to be a limited and selective ganglioneuropathy. Its etiology has not been fully elucidated. Autonomic findings may also accompany. We wanted to present our 25-year-old patient who was diagnosed with Ross syndrome and presented with complaints of inability to sweat, heat intolerance, headache, diarrhea and chronic cough. Keyword: cough, tonic pupil, anhidrosis, compensatory.

Sarcoidosis-Associated Sensory Ganglionopathy and Harlequin Syndrome: A Case Report.

Background and Objectives: Sensory ganglionopathy is a rare neurological disorder caused by degeneration of the neurons composing the dorsal root ganglia. It manifests as various sensory disturbances in the trunk, proximal limbs, face, or mouth in a patchy and asymmetrical pattern. Harlequin syndrome is characterized by unilateral flushing and sweating of the face, neck, and upper chest, concurrent with contralateral anhidrosis. Here, we present and discuss a clinical case of sarcoidosis-associated ganglionopathy and Harlequin syndrome. Case presentation: A 31-year-old woman complained of burning pain in the right side of the upper chest and the feet. She also experienced episodes of intense flushing and sweating on the right side of her face, neck, and upper chest. Three years before these symptoms began, the patient was diagnosed with pulmonary sarcoidosis. On neurological examination, sensory disturbances were present. In the trunk, the patient reported pronounced hyperalgesia and allodynia in the upper part of the right chest and some patches on the right side of the upper back. In the extremities, hypoalgesia in the tips of the fingers and hyperalgesia in the feet were noted. An extensive diagnostic workup was performed to eliminate other possible causes of these disorders. A broad range of possible metabolic, immunological, and structural causes were ruled out. Thus, the final clinical diagnosis of sarcoidosis-induced sensory ganglionopathy, small-fiber neuropathy, and Harlequin syndrome was made. Initially, the patient was treated with pregabalin and amitriptyline, but the effect was inadequate for the ganglionopathy-induced pain. Therefore, therapeutic plasma exchange as an immune-modulating treatment was selected, leading to partial pain relief. Conclusions: This case report demonstrates the possible autoimmune origin of both sensory ganglionopathy and Harlequin syndrome. It suggests that an autoimmune etiology for these disorders should be considered and the diagnostic workup should include screening for the most common autoimmune conditions.

Autism spectrum disorder in a boy with congenital insensitivity to pain with anhidrosis: a case report.

BACKGROUND: In this case report, we described the past history, clinical manifestations, genetic characteristics and cognitive evaluation of a boy with congenital insensitivity to pain with anhidrosis (CIPA) who developed autism spectrum disorder (ASD). CASE PRESENTATION: The boy had an early onset of CIPA at the age of 48 months, and was later diagnosed with ASD at 5 years old. Developmental delays in communication, social skills and the presence of maladaptive behaviors were observed in the patient. Professional treatments significantly improved the developmental delays. CONCLUSIONS: This case demonstrated that ASD may develop in children with CIPA, and pediatricians should be aware that if they suspect or identify a child with CIPA that they should also be screened for ASD using similar examination and diagnostic tools as shown in the present report. Moreover, therapeutic interventions for ASD was helpful for the remission of both diseases.

Mini-Review on the Harlequin Syndrome-A Rare Dysautonomic Manifestation Requiring Attention.

Harlequin syndrome (HS) is a rare autonomic disorder. The causes and risk factors of the disease are not fully understood. Some cases of HS are associated with traumatic injuries, tumors, or vascular impairments of the head. Symptoms of HS can also occur in some autoimmune disorders, ophthalmic disorders, sleep disorders, and with certain organic lesions. In this context, a thorough review of the pathophysiology of HS in relation to neurological, ophthalmological, and dermatological conditions is necessary. In this mini-review, we aim to review the pathophysiological changes and underlying mechanisms in primary and secondary HS. Additionally, we discuss possible management approaches for patients with HS in light of the discussed pathological mechanisms. The main symptoms of HS that are correlated with autonomic nervous system impairments include sudden unilateral flushing of the face, neck, chest, and rarely arm, with concurrent contralateral anhidrosis. Despite reported co-occurring syndromes (such as cluster headaches), several studies have shown that HS could frequently overlap with other syndromes that are disruptive to the idiopathic nerve pathways. HS usually does not require any medical treatment. In some severe cases, symptomatic treatments could be needed. However, total symptomatic relief may not be achieved in many cases of HS. We therefore suggest an approach to comprehensive management of HS, which may lead to better long-term control of HS.

Acquired idiopathic generalized anhidrosis: A case series of two Caucasian patients.

Acquired idiopathic generalized anhidrosis (AIGA) is a rare disorder characterized by insidious or sudden onset of the inability to sweat involving >25% of body surface area in the absence of other neurologic or sweat gland abnormalities and typically affects young, healthy, Asian men. Here, we describe two Caucasian teenagers with the diagnosis. They both had variable responses to prednisone, one in the setting of an elevated ANA, suggesting an autoimmune or inflammatory pathomechanism of the disorder. It is essential the clinician recognizes this rare entity and initiates timely intervention to prevent the serious consequences of hyperpyrexia.

Harlequin syndrome in a young girl: An opportunity to rethink the terminology.

Harlequin syndrome is a rare disorder of the autonomic nervous system, presenting as unilateral reduced flushing and sweating of the face induced by exercise, stress, or heat. It is caused by a cervical sympathetic deficit located at the preganglionic or postganglionic level on the non-flushing side. We present a case of an 8 year old with harlequin syndrome and review the other dermatological conditions for which the term "harlequin" is part of the nomenclature.

Bilateral harlequin syndrome, unilateral Horner syndrome, and Riga-Fede disease as presenting features of hereditary sensory and autonomic neuropathy type IV.

Hereditary sensory and autonomic neuropathy (HSAN) type IV, also known as congenital insensitivity to pain with anhidrosis (OMIM 256800), is part of a family of neurodegenerative disorders that manifest with variable sensory and autonomic neuropathies. In this report, we present a unique dermatological finding in a patient with HSAN type IV: bilateral harlequin syndrome that occurred in association with unilateral Horner syndrome, traumatic alopecia and Riga-Fede disease.

Successful treatment of idiopathic Harlequin Syndrome with oxybutynin and propranolol.

Harlequin syndrome (HS) is a rare entity derived from the dysfunction of the sympathetic nervous system. It is characterised by unilateral facial flushing and sweating induced by exercise, heat and emotion. Most cases are primary with an unknown pathogenic mechanism. In these cases, the prognosis is favourable. Medical or surgical treatments are not usually required for idiopathic HS. However, symptomatic treatment may be indicated when symptoms affect the quality of life of patients. We present the case of a patient with idiopathic HS successfully treated with oxybutynin and propranolol. In this patient, a marked improvement in both hyperhidrosis and facial erythema was noted with this combined therapy. We consider it of interest to highlight the response of our patient to the treatment employed, which may be advantageous in future cases of this rare disorder.

Sudomotor Dysfunction.

Disorders of sudomotor function are common and diverse in their presentations. Hyperhidrosis or hypohidrosis in generalized or regional neuroanatomical patterns can provide clues to neurologic localization and inform neurologic diagnosis. Conditions that impair sudomotor function include small fiber peripheral neuropathy, sudomotor neuropathy, myelopathy, α-synucleinopathies, autoimmune autonomic ganglionopathy, antibody-mediated hyperexcitability syndromes, and a host of medications. Particularly relevant to neurologic practice is the detection of postganglionic sudomotor deficits as a diagnostic marker of small fiber neuropathies. Extensive anhidrosis is important to recognize, as it not only correlates with symptoms of heat intolerance but may also place the patient at risk for heat stroke when under conditions of heat stress. Methods for assessing sudomotor dysfunction include the thermoregulatory sweat test, the quantitative sudomotor axon reflex test, silicone impressions, and the sympathetic skin response.

Patient with Cluster Headache and Harlequin Sign - Related or Not?

BACKGROUND: The harlequin sign or syndrome is a rare cranial autonomic condition characterized by unilateral diminished flushing and sweating of the face (and sometimes arm), in response to heat or exercise. It results from autonomic, mainly sympathetic dysfunction. Although the idiopathic form is the most common, underlying structural abnormalities in the head, neck, and thorax need to be excluded. METHODS AND RESULTS: Here, we describe the first case of the combination of primary cluster headache and the harlequin syndrome in a 49-year-old female patient. The patient presented with a first bout of cluster headache with persisting Horner syndrome and new harlequin sign after the bout. Additional neuroimaging did not reveal underlying pathologies. This report provides an overview of cases from the literature and then discusses the association between primary headaches and the harlequin syndrome. Relevant anatomy, diagnostic tools, and therapeutic options are all considered. CONCLUSION: This case reports a rare combination of cluster headache and harlequin sign that warrants further testing to exclude pathology in the brain, neck or mediastinum. It also illustrates the underlying anatomy and physiology of the autonomic nervous system.

Regular sweating activities for the treatment of cholinergic urticaria with or without acquired idiopathic generalized anhidrosis.

Cholinergic urticaria (CholU) decreases affected individuals' quality of life because they must avoid stimuli including exercise and hot bathing. Although case reports have indicated that regular sweating activities are effective for CholU with hypohidrosis, little evidence is available. This retrospective medical record review examined CholU patients who received any form of treatment at our hospital. Twenty-seven cases (78% men; median age 22 years, range 12-70 years) were analyzed. Fourteen (52%) patients had acquired idiopathic generalized anhidrosis (AIGA). Among the 12 patients receiving sweating therapy (4 with, 8 without AIGA), improvement of symptoms was confirmed in 11 (92%; sweating therapy alone: n = 5, with H1 blocker: n = 5, with steroid pulse: n = 1) including 8 (67%) showing complete response (CR). In this sweating-therapy group, CR was achieved by six of the eight (75%) patients without AIGA and two of the four (50%) patients with AIGA. Among the 15 patients without sweating therapy, symptom improvement was observed in 9 (60%; steroid pulse: n = 7, H1 blocker: n = 2) including 1 (7%) achieving CR. Sweating therapy was safely undertaken except in one case in which the patient showed angioedema and anaphylaxis. Regular sweating activities could be a potential therapeutic option for CholU patients.

Detection of subclinical Harlequin syndrome in pediatric patients.

BACKGROUND: Harlequin syndrome presents as differences in facial coloring due to unilateral flushing. This is the result of the inability to flush on the affected side due to the disruption of vasomotor and sudomotor sympathetic activity. The neurologically intact side appears flushed. A 2°C temperature difference between the flushed and nonflushed sides of the face has been detected in patients presenting with Harlequin syndrome. This difference in temperature might be detectable even in the absence of unilateral flushing, and this subclinical manifestation of the syndrome may occur more often than realized. AIM: To measure and compare the difference in the change in temperature on both sides of the face in patients with a thoracic epidural. METHODS: Fifteen pediatric patients receiving thoracic epidurals for the correction of pectus excavatum via Nuss procedure were enrolled. Temperature measurements on each side of the face were collected at three time points: prior to epidural placement in the holding area, one hour after epidural analgesia had been instituted, and after the patient awakened in the recovery area. The primary outcome is whether or not a temperature difference occurred between the two sides of the face over time. RESULTS: Comparing the pre-op temperature change to post-op temperature change for each side of the face, patient 2 had a large increase in temperature on the left side of the face with a decrease in temperature on the right side of the face. The largest observed difference between the changes in temperature from pre-op to post-op between the right and left sides of the face was 1.85°C in patient 2. This was more than two standard deviations from the mean difference in the patient population. Patient 15 also had a large difference in change in temperature from pre-op to post-op between the right and left sides of the face with an observed difference of 1.14°C, although this was not more than two standard deviations from the mean. None of the patients had unilateral facial flushing. CONCLUSION: Asymmetric effects or distribution of local anesthetic used in thoracic epidurals may result in asymmetric blockade of efferent sympathetic nervous system activity. This may cause differences in temperature between the two sides of the face without unilateral flushing. This phenomenon has previously been termed subclinical Harlequin syndrome. Subclinical Harlequin syndrome may be more common than anticipated and may be detected by comparing temperature differences in patients.

A rare entity of acquired idiopathic generalised anhidrosis which has been successfully treated with pulse steroid therapy: Does the histopathology predict the treatment response?

Acquired idiopathic generalised anhidrosis is an uncommon sweating disorder characterized by loss of sweating in the absence of any neurologic, metabolic or sweat gland abnormalities. Although some possible immunological and structural mechanisms have been proposed for this rare entity, the definitive pathophysiology is still un-clear. Despite some successfully treated cases with systemic corticosteroid application, the dose and route of steroid application are controversial. Here, we present a 41-year-old man with lack of genera-lised sweating who has been successfully treated with high dose pulse intravenous prednisolone. We have discussed his clinical and histopathological findings as well as the treatment options in view of the current literature.

Botulinum toxin type D blocks autonomic cholinergic synapses in humans: discussion of a potential therapeutic use.

Based on epidemiological data it was believed that botulinumtoxin type D (BT-D) may not block human cholinergic synapses. We wanted to investigate BT-D's effect on the autonomic cholinergic synapse in humans. For this, we compared in four volunteers intraindividually the hypohidrotic effect of intradermal BT-D and BT-A in Minor's iodine starch sweat test. Altogether, we studied BT-D in doses of 4, 8, 16 and 32MU and BT-A in doses of 2, 4, 8 and 16MU at weekly intervals throughout a period of 13 weeks. All BT doses were diluted in 0.2 ml 0.9% NaCl/H2O. Overall 704 data points were collected. Combined over all four subjects and all four doses BT-D's hypohidrotic effect intensity was half of BT-A's. BT-D's effect peaked around 5 weeks, BT-A's around 7 weeks. BT-D's effect duration was around 12 weeks, of BT-A's was around 14 weeks. For both BT types the hypohidrotic effect was dose dependent. BT-D, when injected intradermally, can block autonomic cholinergic synapses in humans. Compared to BT-A, BT-D's effect intensity was half and its effect duration was some 2 weeks shorter. With its weaker and shorter effect BT-D does not seem to promise therapeutic effects superior to BT-A.